Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking

Yasuko Iwakiri, Ayano Satoh, Suvro Chatterjee, Derek K. Toomre, Cecile M. Chalouni, David Fulton, Roberto J. Groszmann, Vijay H. Shah, William C. Sessa

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182 Citations (Scopus)


Nitric oxide (NO) is a highly diffusible and short-lived physiological messenger. Despite its diffusible nature, NO modifies thiol groups of specific cysteine residues in target proteins and alters protein function via S-nitrosylation. Although intracellular S-nitrosylation is a specific posttranslational modification, the defined localization of an NO source (nitric oxide synthase, NOS) with protein S-nitrosylation has never been directly demonstrated. Endothelial NOS (eNOS) is localized mainly on the Golgi apparatus and in plasma membrane caveolae. Here, we show by using eNOS targeted to either the Golgi or the nucleus that S-nitrosylation is concentrated at the primary site of eNOS localization. Furthermore, localization of eNOS on the Golgi enhances overall Golgi protein S-nitrosylation, the specific S-nitrosylation of N-ethylmaleimide-sensitive factor and reduces the speed of protein transport from the endoplasmic reticulum to the plasma membrane in a reversible manner. These data indicate that local NOS action generates organelle-specific protein S-nitrosylation reactions that can regulate intracellular transport processes.

Original languageEnglish
Pages (from-to)19777-19782
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
Publication statusPublished - Dec 26 2006
Externally publishedYes



  • Endothelial nitric oxide synthase
  • Golgi
  • Targeting

ASJC Scopus subject areas

  • Genetics
  • General

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